Method for manufacturing endo-osseous implants or medical prosthesis by ionic implantation technique

ABSTRACT

The method comprises the ion implantation of controlled quantities of elements such as CO, C or O in endo-osseous implants or prostheses manufactured in metals, metallic alloys or biocompatible compound materials. This surface treatment originates some modifications in the characteristics of the surface of the endo-osseous implants or prostheses which increases significantly their degree of osseointegration.

This application claims the benefit of International Patent ApplicationNo. PCT/ES02/00178 filed 11 Apr. 2002, which claims priority of SpanishPatent Application No. P200100873 filed 16 Apr. 2001.

FIELD OF THE INVENTION

This invention is related, in general, with surface treatments ofimplants and medical prostheses to improve their osseointegrationproperties, in particular, it refers to a method for the production ofendo-osseous implants or prostheses manufactured in a base material andtreated superficially by means of ion implantation with enhancedosseointegration properties.

BACKGROUND OF THE INVENTION

The requirement for prosthetic treatments of long duration (implants orknee, hip, maxillofacial, cranial, etc. prostheses), is increasinglyusual in daily clinical practice, and involves the use, in numerouscases, of metallic materials (subcutaneous or osseous implants) mainlyin patients subjected to major traumatic surgery, maxillofacial surgery,osteoporotic and osteoproliferative patients. The employment of thesesystems of prosthetic substitution is accompanied by a not insignificantimplant failure rate, which in some cases surpasses 30%, and at timesmakes recourse to this technique an impossibility.

The most frequent complications encountered, described in the medicalliterature, are the infectious type (infection of the implant,bacteremia, sepsis, and others less frequent, like gangrene, etc.), theinflammatory type (reaction to a foreign body, local inflammation, totalrejection), those of tissue integration (gingivitis, sinovialmetallosis, osteoresorption) and those arising from their handling anduse (rupture of the bone, failure of the metal-tissue interface).

The biocompatible metals constitute the most important and diverse groupof materials used in biomedical applications because they offerappropriate properties of biocompatibility and chemical inertia whichmake them suitable for contact with biological fluids and tissues. Also,they have the characteristic that they can be manufactured in a greatvariety of ways.

However, the evolution observed in recent years regarding the types ofalloys employed has not reduced the number of complications as much aswould have been expected and the experimental procedures used to improvetheir biocompatibility have been limited to more permeable designs orsurface impregnations, more or less intense, with molecules havingbiological activity (antibiotics, antiseptics, antiaggregants, etc.).

The requirement remains to develop medical materials whose employmentpermits avoidance of the entirety or part of the aforementionedcomplications.

In that concerning the problem of osseointegration of the prostheses orimplants, a method of approaching the problem could consist in applyinga surface treatment thereon which confers upon them the appropriatecharacteristics.

This is the case of ion implantation, a treatment which does not modifythe structural properties or the dimensional tolerances of the treatedprostheses or implants (see FIG. 1) but which, however, can modify theirsurface properties by means of the introduction of a series of selectedelements on the surface, modifying the properties thereof in the desiredsense.

Use has been made of different techniques of ion implantation for manyyears in different fields of application with the object of modifyingthe surface properties of the components. It is used, for example, inelectronics for modification of the electrical properties ofsemiconductors. It is also applied in the metal mechanics industry forthe improvement of properties of resistance to abrasion and corrosion,in cases such as moulds and injection mouthpieces, machining and cuttingtools, gauges, etc.

Ion implantation has also been used on biomaterials. This is the case,for example, of the implantation of germicidal elements in medicalequipment described in U.S. Pat. No. 5,492,763, or the implantation inimplants of cobalt-chromium alloys with the object of increasing surfacehardness and reducing friction as described in European patentapplication EP 526 581. The problem of osseointegration has also beenbroached from the ion implantation technique in order to produce asurface coated with hydroxyapatite, a coating which has also beenapplied by other processes. Such is the case of the method for theproduction of surgical implantations coated with synthetic bonedescribed in Spanish patent ES 2.006.658 which employs high energystreams of xenon to coat the implants with hydroxyapatite by thesputtering or cathodic spraying technique. German patent application DE19830530 describes the production of titanium surfaces coated withcalcium phosphate by ion implantation. In this last case, use is made ofphosphorus and calcium implantation followed by a heat treatment.

Notwithstanding the existence of previous applications of ionimplantation in implants and medical prostheses, the ion implantationmethods employed provide implants and prostheses with insufficientosseointegration properties and/or with a risk of lixiviation of theions to the physiologic medium in contact with the inadequate implantsand prostheses, and/or with not completely satisfactory tribologicalproperties.

SUMMARY OF THE INVENTION

The invention confronts the problem of providing endo-osseous implantsand prostheses, superficially treated by ion implantation, withcharacteristics of enhanced osseointegration.

The solution provided by this invention comprises the development of amethod for the production of said implants and medical prosthesesdesigned to overcome the problems of osseointegration thereof in theosseous structures and is based in that the ion implantation ofcontrolled quantities of certain elements and/or compounds in saidimplants or prostheses, under certain conditions, allows endo-osseousimplants and/or medical prostheses to be obtained with an enhanceddegree of osseointegration thereof, and/or with a reduced degree oflixiviation of ions to the physiological medium, and/or with enhancedtribological properties.

BRIEF DESCRIPTION OF THE FIGURES

In FIG. 1 a simplified diagram of the ion implantation process can beseen. The ions are accelerated by application of high electromagneticfields, and impact on the surface of the material, being inserted in thematerial. This process is carried out without originating anymodification in the surface dimensions of the implanted material, butnevertheless its physico-chemical properties are modified.

In FIG. 2 detail of an embodiment is shown in which the beam of ionsimpacts directly on a dental implant, at the same time as the latter issubjected to a rotational movement. The beam can impact the piece fromdifferent directions, so that it is assured that the whole surface ofthe implant is subjected to the ion implantation treatment.

In FIG. 3 a simplified schematic of a typical process for manufacturingdental implants can be seen.

FIGS. 4 and 5 show the aspect of a cross-section of the implants largelysurrounded by osseous matter. The samples were prepared have withMartins and Masson staining, respectively.

FIG. 6. is a chart indicating the bone implant contact percentage (CHI)of dental implants implanted in the epiphyseal area (distal), anuntreated control implnat and a CO ion treated implant are represented.

FIGS. 7 and 8 are photographs taken with a sweeping electronicmicroscope, in which the close contact can be observed of the osseousmatter with the surface of the implant which has been subjected to ionimplantation treatment.

FIGS. 9, 10, 11 and 12 are some photographs taken with a sweepingelectronic microscope which show different details at differentmagnifications of the osseous structure after removal of the treatedimplant.

In FIG. 13 the XPS spectrum is shown, with the bonding energies of theelements present in the atomic layers of the bone-implant interface, ofa sample subjected to the ion implantation treatment.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides a method for the production of endo-osseousimplants or medical prostheses, hereinafter method of the invention,said endo-osseous implants or medical prostheses being manufactured froma base material, by means of a surface ion implantation treatment of, atleast, an element selected among the elements C, O, H, Xe, Ar, He, Kr,Ne and/or a compound which comprises one or more of said elements, inwhich an ion beam energy is used of between 1 keV and 1 MeV, in whichthe process of ion implantation is carried out in a vacuum chamber witha vacuum better than 10⁻³ millibars and a dose is applied of, at least,10¹⁵ ions/cm².

The term endo-osseous implants or medical prostheses, as it is employedin this description includes whatever endo-osseous implant or prosthesesintended to be in contact with living tissues or cells, or with corporalor biological fluids.

As base material use can be made of any metal, metallic alloy,biocompatible material, and mixtures thereof, employed in theelaboration of endo-osseous implants and/or medical prostheses, such asthose materials which satisfy the standard UNE-EN ISO 10993. In aparticular embodiment, said base material is selected among titanium;alloys of titanium, aluminium and vanadium, for example, Ti-6Al-4V;alloys of chromium and cobalt (Cr—Co); alloys of cobalt, chromium andmolybdenum (Co—Cr—Mo), stainless steel, for example, AISI 316 stainlesssteel, etc.

The method of the invention comprises the implantation of, at least, anion of an element selected among the elements C, O, H, Xe, Ar, He, Kr,Ne and/or of an ion of a compound which comprises one or more of saidelements, for example, CO, CO_(n), CxHy, etc. (where n is an integerbetween 1 and 2, and x and y are integers between 1 and 100.)

The method of the invention is carried out, advantageously, in atreatment or vacuum chamber with a vacuum level of, at least, 10⁻³millibars.

Ion implantation, according to the method of the invention, can becarried out, optionally, in presence of a residual atmosphere in saidvacuum chamber. This residual atmosphere can consist both in thepresence of oxygen and of residual organic compounds, for example,organic compounds produced by the evaporation of an organic compoundduring the process of ion implantation in the treatment chamber. Theimplanted ionic doses can vary within a wide range depending on thenature of the implanted ion, being, in general, greater than 10¹⁵ions/cm² with the object of providing the endo-osseous implant or themedical prostheses with the necessary properties to achieve asignificant enhancement of the osseointegration capacity.

The process of ion implantation according to the method of the inventioncan be carried out over a wide temperature range, for example, it can becarried out at a temperature between −120° C. and 800° C., preferably,between ambient temperature and 250° C. In a particular embodiment, withthe object of favouring mechanisms for diffusion, precipitation ortransformation of compounds, the process of ion implantation accordingto the method of the invention can be carried out at a temperature ofbetween 250° C. and 800° C. In other applications, these same mechanismsfor diffusion, precipitation or transformation can be achieved by meansof heat treatment of the endo-osseous implants or prostheses, when theprocess of ion implantation has been completed, at a temperature ofbetween 250° C. and 800° C.

The ion implantation treatment, according to the method of theinvention, can be applied to endo-osseous implants or medical prosthesesby means of techniques of line of sight ion implantation or beam ionimplantation, plasma immersion ion implantation or plasma source ionimplantation, or by means of whatever other equivalent technique.

As a result of the method of the invention endo-osseous implants ormedical prostheses can be obtained, for example, dental implants,prostheses of hip, knee, etc., with an enhanced degree ofosseointegration thereof, and/or with a reduced degree of lixiviation ofions to the physiological medium in contact with said implants and/orprostheses, and/or with enhanced tribological properties, for example,better resistance to abrasion, decreased friction, etc.

The endo-osseous implants and prostheses attainable by means of themethod of the invention constitute an additional object of thisinvention. In a particular embodiment, said endo-osseous implants orprostheses have an enhanced degree of osseointegration, and/or a reduceddegree of ionic lixiviation to the physiologic medium in contact withthe implant or the prostheses, and/or enhanced tribological properties.

The following example of embodiment illustrates the invention and shouldnot be taken restrictively with regard to the scope thereof.

EXAMPLE Ion Implantation of CO⁺ Ions in a Dental Implant

This example illustrates the application of a surface ion implantationtreatment of CO⁺ ions in a dental implant manufactured in a titaniumalloy Ti6Al4V. For it, 8 Spline Twist TiTM (Sulzer Calcitek Inc.)commercial dental implants were selected, 8 mm long by 3.75 mm diameter.They are smooth-surface machined screws manufactured in Ti6Al4V. For thesubsequent tests, other 8 dental implants of the same batch werereserved without treatment. In FIGS. 4 and 5 the appearance of thesescrews can be seen in cross-section.

The dental implants were cleaned successively in an ultrasonic bath ofacetone and ethanol for a minimum period of time of 5 minutes.Subsequently they were all introduced in the vacuum chamber. The vacuumlevel that was reached and maintained during the entire ion implantationprocess was at all times better than 5.10⁻⁷ millibars.

The ion implantation treatment was carried out in an Ion Implanter ofthe 1090 series by Danfysik AS, located in the facilities of Inasmet inIrun. The dental implants were implanted ionically with CO⁺ ions, at anenergy of 50 keV with a dose of 5.10¹⁷ ions/cm². This treatment wasapplied to the lateral cylindrical surface and the end surface of thethread of the dental implants. The temperature of the dental implantsdid not reach at any time values of more than 170° C.

In FIG. 1 a simplified schematic of a typical manufacturing process ofdental implants can be observed.

According to estimates made with the “Profile Code” software package,the element implanted under these conditions is in regions of less than0.1 μm in depth, atomic concentrations being reached of more than 25%for both elements in the areas of maximum concentration and normalincidence of the ion beam.

The treatment of dental implants by the ion implantation techniquedescribed above allows the implant failure rate to be reduced, due to anincrease in the degree of osseointegration of the dental implants in theosseous mass. This has been demonstrated by means of osseousimplantation tests.

Osseous Implantation Test

Screws of Ti6Al4V with CO⁺ ion implantation have been tested by means ofthe “bone implantation test” according to standard UNE-EN 10993-6:1995.

The objective of this test was to evaluate the biological response ofthe osseous tissue to the implanted material. The method compares thebiological response to implants in test samples with the biologicalresponse to implants in control samples.

Animals

Rabbits were used, mature male albinos (New Zealand White), animal modelwith osseous structures of sufficient mass to receive the dentalimplants, the mean weight of which was 4700 g, with a minimum of 4000 gand a maximum of 5200 g. They have been kept and cared for according tothe ISO 10993-2:1992 standard and in compliance with the legalregulations of the Ministry of Agriculture, Fishing and Foodstuffs RD223/1988, Order dated Oct. 13, 1989.

Samples

8 smooth-surface machined screws manufactured in Ti6Al4V, 8 mm long by3.75 mm diameter, and implanted ionically with CO⁺ according to thepreviously described procedure.

Control

8 smooth-surface machined screws manufactured in Ti6Al4V, 8 mm long by3.75 mm diameter, similar to the samples were used as control samples.

Place of Implantation

4 screws per rabbit implanted in the tibial plateau.

Operating Procedure

A general anaesthesia was applied with tiacine hydrochlorate of 3.15mg/500 g intramuscular (i.m.) (ROMPUN 2%®) and ketamine 18 mg/500 g i.m.(KETOLAR 50®), completed with local anaesthesia in the intervention areawith lidocaine 1:100.000, 1 ml in each leg. After shaving anddisinfection of the area, deferred cutaneous incision was carried out,with sterile technique, separation of the fascias and distal inserts ofthe internal straight and semi-tendinous muscles and of the proximalinsert of the cranial tibial muscle and detachment of the periosteum ofthe front face of the proximal epiphysis of both tibias.

With micromotor and cooling with physiological serum, the osseouscortical mass was drilled at 1500 revolutions/minute, using a ball bit.Next, the implant osseous channel was deepened to 8 mm with bits withexternal cooling of 2 mm in diameter and internal of 3 mm and bit of 3.3mm in diameter, with external irrigation, followed by diestock. Theionically implanted and control dental implants were placed in thechannel by manual insertion employing a ratchet key. The wound wasclosed by planes with polyglactin suture 4/0 (Vycril®) and the skin withsilk 3/0 (Aragó®).

Antibiotic prevention was administered with benzylpenicillin benzathine50×10³ U/kg/week i.m. (BENZETACIL 1.200.000®). Locally, after shavingthe paws at the level of the tibial plateaux, iodized povidone(Betadine®) was applied on the area. During the following days analgesictreatment was administered with acetil salicylate of lysine 10 mg/500 g,i.m. (INYESPRIN®). In the days following, the areas of the surgicalwounds were cleaned and 0.12% chlorhexidine and antibiotic ointment(Furacin®) was applied locally.

The animals remained for three months housed individually in acontrolled medium with light/darkness cycles (12 h), air conditioning(15 renovations/h) and at a temperature controlled between 18° C. and22° C., complying with the legal regulations in this respect.

After sedation with diazepam 5 mg/kg i.m. (Valium®), the animals weresacrificed using a carbon monoxide chamber, the tibial plateauxcontaining the implants were extracted in block and introduced in 4%formol for later processing thereof.

The osseous blocks, containing the implants, were subjected to atechnique of desiccation and dehydration in 60%, 80%, 96% and 100%acetones and alcohols, concluding in 100% xylol. Later separation,cutting and fine polishing were carried out according to the DONATHtechnique, for obtaining histological sections. To make microscopicstudy possible, the samples were subjected to staining. An example ofthe appearance of these samples can be seen in FIGS. 4 and 5.

Appraisal of Results 1. Histological Evaluation

The evaluation of the histological preparations was done by means ofprior capture of images with a digital macrophotography system (Nikon).The images so obtained were analysed by means of an Omnimet imageanalyser, and processed with an image handling program Adobe Photoshop5.0.

When defining the osseointegrated area the following criteria wereadopted:

-   -   The area in contact with spongy or trabecular bone was not        considered osseointegrated, only that with cortical bone.    -   The adjacent areas were considered osseointegrated which for        contour similarity with the cortical bone could be assumed to        have been displaced in the preparation process.    -   Those areas were considered osseointegrated which, in a computer        amplification of the area (×200) showed small and fine layers of        cortical osseous tissue adhered to the implant.    -   Considered as osseointegrated as a single area were those        adjacent integrated areas, the separation distance of which was        less than one quarter of the width of the thread of the implant.

The results showed statistically significant differences between theimplants located on the tibia of the rabbit in the epiphyseal area(distal) or metaphyseal area (mesial), osseointegration being moredifficult in the first case, as it concerns an area poorer in corticalbone. In this last case, a significantly greater bone-implant union wasappreciated in the case of implants with ion implantation treatment, ascan be observed in FIG. 6.

2. Study by Means of Electronic Microscopy

The type of union was analysed between the bone and the implant. InFIGS. 7 and 8 a close contact can be observed between bone and implantat different magnifications. The whiter images correspond to bone andthe darker to soft tissue. This was checked by a composition analysis byelectron microprobe (EDS) of both areas.

Also, in one of the samples the implant of the histological section wasremoved and the bone observed from the cavity of the implant. The imagesallow the osseous structure in contact with the implant to be seenclearly (see FIGS. 9, 10, 11 and 12).

3. Study by Means of XPS

By means of this technique the composition of the elements present inthe atomic layers of the bone-implant interface was analysed, and thetype of linkage between the titanium and the osseous tissue to which itis joined (FIG. 13).

It was observed that maximum energy was at a binding energycorresponding to a Ti—O—C bond, where the carbon belonged to a complexorganic molecule. Said Ti—O—C bond present in the interface of thesurface of the implant corresponds to the protein-metallic oxide unionformed during the period of permanency in the living animal.

CONCLUSION

Surface ion implantation treatment with CO⁺, induces changes in physicalstructure and surface electrochemistry, increasing adhesion to thesurrounding biological tissue.

The histomorphometric results obtained confirm the improvement inosseointegration, in terms of bone implant contact.

Additionally, ionic implantation improves tribological properties,increasing the resistance of the material treated to wear and abrasion,it increases resistance to corrosion and chemical attack, reducing thepossibility of electrochemical reaction with the medium, thereforediminishing lixiviation of the material.

What is claimed:
 1. A surface treatment method for the production ofendo-osseous implants or medical prostheses, said endo-osseous implantsor medical prostheses being manufactured from a base material, by meansof a surface ion implantation treatment of CO and/or a compound whichcomprises CO, e.g., C_(a)O_(b)H_(c) or C_(a)O_(b)H_(c)N_(d) in which anion beam energy is employed of between 1 keV and 1 MeV, in which theprocess of ion implantation is carried out in a treatment chamber with avacuum better than 10⁻³ millibars and a dose is applied of, at least,10¹⁵ ions/cm².
 2. Method according to claim 1, in which said basematerial is selected among a metal, a metallic alloy, a biocompatibleceramic, and mixtures thereof, i.e. composites employed in theelaboration of endo-osseous implants and/or medical prostheses. 3.Method according to claim 2, in which the process of ion implantationtakes place in presence of a residual atmosphere of oxygen or of organiccompounds in the treatment chamber.
 4. Method according to claim 3, inwhich an organic compound is evaporated during the process of ionimplantation in the treatment chamber.
 5. Method according to claim 4,in which the process of ion implantation is applied on said endo-osseousimplants or medical prostheses by means of techniques of line of sightion implantation or beam ion implantation, plasma immersion ionimplantation or plasma source ion implantation, or ion bombardmenttechniques.
 6. Method according to claim 5, in which the process of ionimplantation is carried out at a temperature between −120° C. and 800°C.
 7. A surface treatment method for the production of endo-osseousimplants or medical prostheses, said endo-osseous implants or medicalprostheses being manufactured from a base material, by means of asurface ion implantation treatment of CO and/or a compound whichcomprises CO, e.g., C_(a)O_(b)H_(c) or C_(a)O_(b)H_(c)H_(d) in which anion beam energy is employed of between 1 keV and 1 MeV, in which theprocess of ion implantation is carried out in a treatment chamber with avacuum better than 10⁻³ millibars and a dose is applied of, at least,10¹⁵ ions/cm². in which the endo-osseous implants or the prosthesesundergo a thermal treatment at a temperature of between approximately250° C. and 800° C. after the process of ion implantation.
 8. Anendo-osseous implant or medical prostheses, where at least the surfacesto be in contact with bone are treated, by the method of claim
 1. 9.Endo-osseous implant or medical prostheses according to claim 8, inwhich said implant or prostheses has an enhanced degree ofosseointegration.
 10. Method according to claim 9 for dental implantswherein said osseointegration is typically increased from around 50% toaround 80% in poor bone areas, and/or a reduced degree of ioniclixiviation to the physiologic medium in contact with the implant or theprostheses.